Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia

Yoshihiro Inamoto; Mary E D Flowers; Tao Wang; Alvaro Urbano-Ispizua; Michael T Hemmer; Corey S Cutler; Daniel R Couriel; Amin M Alousi; Joseph H Antin; Robert Peter Gale; Vikas Gupta; Betty K Hamilton; Mohamed A Kharfan-Dabaja; David I Marks; Olle T H Ringdén; Gérard Socié; Melhem M Solh; Görgün Akpek; Mitchell S Cairo; Nelson J Chao; Robert J Hayashi; Taiga Nishihori; Ran Reshef; Ayman Saad; Ami Shah; Takanori Teshima; Martin S Tallman; Baldeep Wirk; Stephen R Spellman; Mukta Arora; Paul J Martin

doi:10.1016/j.bbmt.2015.05.023

Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia

Biol Blood Marrow Transplant. 2015 Oct;21(10):1776-82. doi: 10.1016/j.bbmt.2015.05.023. Epub 2015 May 30.

Authors

Yoshihiro Inamoto¹, Mary E D Flowers², Tao Wang³, Alvaro Urbano-Ispizua⁴, Michael T Hemmer⁵, Corey S Cutler⁶, Daniel R Couriel⁷, Amin M Alousi⁸, Joseph H Antin⁶, Robert Peter Gale⁹, Vikas Gupta¹⁰, Betty K Hamilton¹¹, Mohamed A Kharfan-Dabaja¹², David I Marks¹³, Olle T H Ringdén¹⁴, Gérard Socié¹⁵, Melhem M Solh¹⁶, Görgün Akpek¹⁷, Mitchell S Cairo¹⁸, Nelson J Chao¹⁹, Robert J Hayashi²⁰, Taiga Nishihori¹², Ran Reshef²¹, Ayman Saad²², Ami Shah²³, Takanori Teshima²⁴, Martin S Tallman²⁵, Baldeep Wirk²⁶, Stephen R Spellman²⁷, Mukta Arora²⁸, Paul J Martin²

Affiliations

¹ Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. Electronic address: yinamoto@ncc.go.jp.
² Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
³ Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
⁴ Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS and Institute of Research Josep Carreras, Barcelona, Spain.
⁵ Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
⁶ Center for Hematologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
⁷ Department of Medicine, University of Michigan, Ann Arbor, Michigan.
⁸ Division of Cancer Medicine, Department of Stem Cell Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
⁹ Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College of London, London, United Kingdom.
¹⁰ Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
¹¹ Blood and Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
¹² Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
¹³ Pediatric Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom.
¹⁴ Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation, Stockholm, Sweden.
¹⁵ Department of Hematology, Hospital Saint Louis, Paris, France.
¹⁶ Blood and Marrow Transplant Center, Florida Hospital Medical Group, Orlando, Florida.
¹⁷ Stem Cell Transplantation and Cellular Therapy Program, Banner MD Anderson Cancer Center, Gilbert, Arizona.
¹⁸ Department of Pediatrics, New York Medical College, Valhalla, New York.
¹⁹ Division of Cell Therapy and Hematologica, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
²⁰ Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
²¹ Department of Medicine, Abramson Cancer Center, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
²² Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
²³ Division of Hematology/Oncology, Department of Pediatrics, Mattel Children's Hospital at University of California Los Angeles, Los Angeles, California.
²⁴ Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
²⁵ Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
²⁶ Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington.
²⁷ Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, Minneapolis.
²⁸ Division of Hematology, Oncology, Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota.

Abstract

Combinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality. TAC+MTX was used more frequently in older patients and, in recent years, in both SIB and URD groups. In multivariate analysis, TAC+MTX was associated with a lower risk of mortality in URD recipients and with slightly earlier absolute neutrophil count recovery in SIB recipients. Other outcomes did not differ statistically between the 2 regimens. No firm conclusions were reached regarding the relative merits of TAC+MTX versus CSP+MTX after hematopoietic cell transplantation for acquired aplastic anemia. Prospective studies would be needed to determine whether the use of TAC+MTX is associated with lower risk of mortality in URD recipients with acquired aplastic anemia.

Keywords: Aplastic anemia; Cyclosporine; Graft-versus-host disease; Hematopoietic cell transplantation; Immunosuppression; Tacrolimus.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Age Factors
Anemia, Aplastic / therapy*
Cyclosporine / therapeutic use*
Drug Therapy, Combination
Female
Graft Survival
Graft vs Host Disease / epidemiology
Graft vs Host Disease / prevention & control*
Hematopoietic Stem Cell Transplantation / adverse effects*
Humans
Immunosuppressive Agents / therapeutic use*
Living Donors
Male
Methotrexate / therapeutic use
Proportional Hazards Models
Retrospective Studies
Tacrolimus / therapeutic use*
Transplantation Conditioning / methods
Treatment Outcome

Substances

Immunosuppressive Agents
Cyclosporine
Tacrolimus
Methotrexate

Abstract

Publication types

MeSH terms

Substances

Grants and funding